(-)Deprenyl is a selective inhibitor of monoamine oxidase (MAO) type B. MAO B uses as preferential substrates phenylethylamine and dopamine, while MAO A preferentially catabolizes norepinephrine (NE), dopamine and serotonin (5HT). At a dose of 5 mg per day, which selectively inhibits the MAO B, (-)deprenyl relieved many symptoms of depressed patients without eliciting the strong side-effects induced by other MAO inhibitors. In rats receiving (-)deprenyl (L Mumol/kg, s.c., for 21 days) the NE-stimulated cAMP accumulation and the Beta-adrenergic receptor number in minces and crude synaptic membranes from frontal cortex were significantly decreased. Moreover after the same treatment schedule the number of 3H-imipramine recognition sites in frontal cortex and hippocampus was significantly increased. Interestingly, (-)deprenyl is not active "in vitro" as a displacer of 3H-imipramine specifically bound to rat brain membranes and also the possibility that this effect is due to the formation of one of the (-)deprenyl metabolites, amphetamine, or to the blockade of MAO3B was ruled out. A selective lesion of the 5HT axon terminals prevented the increase of H-imipramine binding and the attenuation of the Beta-adrenergic-coupled cAMP generating system evinced by repeated injections of (-)deprenyl. Our results suggest that (-)deprenyul possesses many actions that are proper of antidepressants and by a primary modification of the serotonergic neurons can determine those modifications of the noradrenergic function that are believed to be beneficial to depressed patients.